Gene therapy
Casually, viruses have been paraphrased as "jumping genes" or "bad news in an envelope". Both references acknowledge their potential for gene therapeutic applications. From an opposite vantage point, a host species may profit from a virus as a population control agent, as a biological weapon that destroys competitors for limited natural resources by means of what we may flippantly call "contagious gene therapy"; these viruses may occasionally wreak havoc when a species is targeted, which did not undergo co-evolutionary adaptation (Table 3).

However, a virus infection may also be looked at more favourably, as a special form of "gene therapy". The host acquires the genome of an infecting virus, and in the course of the ongoing virus-host interactions, a plethora of host genes is regulated. This occurs in a variety of manners, depending on the virus and the infected organism, and includes the multifaceted cascade of immune responses (see e.g. [11,30]. Ultimately, the infected organism will not only survive but also have acquired a selective advantage through an improved immune defence. In a long-term perspective, such virus-host interactions lead into the mentioned co-evolutionary pathway, with advantages on both sides. Thus viruses may also be viewed as movable genes or extrinsic genotypes of a host. At the same time, the virus profits from this mutuality by constantly probing for the opening of new ecological niches. In this case, the virus cannibalises genomic information from its host and modifies it in a manner that suits its replication and survival in nature.

From this perspective, the virus could be looked at as a companion, a helping hand, and it would seem plausible to ask one's friend for even more help. Recently, Luo and Salzman (2000) have compared the efficiency with the toxicity of DNA delivery systems [16]. They found that most often efficient delivery was obtained only at the expense of high toxicity (Fig. 3). The lowest relative toxicity associated with the highest efficiency was accredited to microinjection. Needless to say that viruses easily surpass the efficiency of manual microinjection.

In Table 4 I have listed some advantages and disadvantages of viral vectors. In most cases advantages in one aspect are counterbalanced by disadvantages in other aspects.

Collaborative efforts between clinicians, gene therapy specialists and virologists have resulted in helpervirus-free vectors, which combine the advantages of different systems [6,20]. For example the large transgene capacity of up to 160 kbp and ability to target neuronal cells of herpes simplex virus amplicons was successfully combined with elements of the adeno-associated virus (AAV), which stands for sustained gene expression and the possibility to integrate the transgene at a specific location of the human chromosome 19 [7]. Moreover, a herpes simplex virus-Epstein-Barr virus hybrid amplicon was used to convert cells to producers of retrovirus vectors, which were enveloped for either ectotropic or amphotropic cell targeting in gene therapeutic applications [21].

These vectors are not only tools for the treatment of humans suffering from certain genetic diseases. They may be important for the analysis and modification of virus-host interactions in general. Thus herpetic stromal keratitis (HSK) is considered as virus-induced but sustained by the immune system [27]. The ongoing ocular inflammation can be suppressed by the topical administration of IL-10 DNA [8]. This report indicated that ongoing immunopathological events can be influenced by local gene therapy. There is an enormous potential for helpervirus-free amplicon vectors to modulating immunopathological diseases. By using them for gene delivery, most caveats associated with conventional viral vectors, as listed in Table 4, would appear manageable.

This may seem a truism, but I still want to emphasise: an enormous amount of virological knowledge will have to be collected before such visionary concepts will find their way into medical or veterinary applications.

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